For hereditary enzyme deficiency, for which no radical treatments have been known to date, enzyme replacement therapy in which an enzyme is produced by genetic engineering and is then administered in a blood vessel by intravenous drip or the like has been developing. As an example of hereditary enzyme deficiency whose prevalence is relatively high and which is designated as a specified disease (intractable disease), Fabry disease (hereditary α-galactosidase deficiency, which is one of a group of genetic diseases and also called lysosomal disease), is well known (refer to Kenneth J. Dean et al., Fabry Disease, “Practical Enzymology of the Sphingolipidoses”, U.S.A., Aln R. Liss, Inc., 1997, p. 173-216).
Fabry disease is a glycolipid metabolic disorder which develops as follows: As a result of a decrease in the activity of an enzyme called “α-galactosidase”, which is one of the enzymes present in a lysosome, which is one of the human intracellular organelles, and deficiency of the enzyme, a glycolipid called globotriaosylceramide (also referred to as ceramide trihexoside), which is an in vivo substrate of the enzyme, is not decomposed and accumulated in the body (for example, blood vessels, skins, cornea, nerves, kidneys, and heart).
Since a gene encoding α-galactosidase lies on the X chromosome, this disease has a mode of X-chromosomal inheritance. Therefore, in this disease, a definite clinical feature is observed mainly in hemizygote in males. It is believed that “classic Fabry disease”, which takes a typical clinical course, develops in about one out of 40,000 male children. Symptoms such as pain in the hand and the foot, hypohidrosis, angiokeratoma, and corneal opacity appear during the juvenile term and adolescence; these symptoms progress and then cause systemic organ damage such as renal failure, heart failure, and cerebrovascular disorder during middlescence and thereafter; and these become the cause of death. In addition, a disease which does not take such a typical clinical course as “classic Fabry disease” and which develops late and takes a relatively moderate course, is “variant Fabry disease”. In patients having this type of disease, residual α-galactosidase activity is observed though it is low. As a variant Fabry disease, for example, “cardiac Fabry disease” is known. The above-mentioned glycolipid accumulation mainly occurs in the heart. Thereby, cardiac hypertrophy occurs, and disorders such as heart failure and arrhythmia are caused. On the other hand, in female heterozygote Fabry patients, various types of clinical features are observed in accordance with the characteristics of the X chromosome. Specifically, cases ranging from serious cases which are similar to those of hemizygote in males to cases in which substantially no symptoms are observed exist. However, according to recent research, it has become clear that most female heterozygote Fabry patients develop some symptoms when they become old. There is a viewpoint that they should be treated not as “carriers” but as “patients”.
Recently, enzyme replacement therapy for Fabry disease has also been established, and a recombinant human α-galactosidase produced in a cell derived from mammals has been widely used as an active ingredient of a Fabry disease therapeutic agent in the above therapy (refer to Eng C M et al., Am J Hum Genet, 68: 711-722 (2001); Eng C M et al., N Engl J Med, 345: 9-16 (2001); and Schiffmann R et al., Proc Natl Acad Sci USA, 97: 365-370 (2000)).
Furthermore, a method in which a recombinant human α-galactosidase produced using a cell (for example, yeast) other than an animal cell as a host is used for the medical treatment (enzyme replacement therapy) of Fabry disease (refer to Japanese Unexamined Patent Application Publication No. 2002-369692), a gene therapeutic method in which an enzyme is replaced by introducing a gene encoding human α-galactosidase into a cell of an affected tissue to express the gene (refer to Japanese Unexamined Patent Application Publication (Translation of PCT Application) No. 2002-522509), and the like have also been proposed.